Depression in Pregnancy- Nonpharmacologic Tx

Unipolar Depression During Pregnancy: Nonpharmacologic Treatment Options

Christopher Tjoa; Emmanuelle Pare; Deborah R Kim

Posted: 07/12/2010; Women's Health. 2010;6(4):565-576. © 2010 Future Medicine Ltd.

Abstract and Introduction

Abstract

Depression during pregnancy can negatively affect maternal and fetal health. Some women will choose not to take psychotropic medications during pregnancy. This article reviews alternatives to pharmacologic treatments for women suffering from unipolar depression during pregnancy, focusing on exercise therapy, phototherapy, transcranial magnetic stimulation and acupuncture.

Introduction

Depression during pregnancy affects approximately 13% of pregnant women, making it a national health issue of vital importance. [1] Treating depression in pregnant women is a difficult clinical problem given the concern regarding how treatments may affect the developing fetus. [2] Many women prefer not to take antidepressants during pregnancy and healthcare practitioners may be reluctant to prescribe them. For women who prefer not to take antidepressants, other options need to be made available. This review introduces and discusses nonpharmacologic treatment alternatives for women suffering from antepartum depression.

Depression

Major depressive disorder (MDD) is a common psychiatric disorder characterized by episodic decreases in mood and anhedonia capable of causing vegetative symptoms such as fatigue, insomnia and decreased appetite. [3] MDD ranges in severity from mild depression – consisting of minor impairment in occupational/social functioning – to severe, characterized by the high likelihood of suicidal ideation, possible psychotic symptoms (including delusions and hallucinations) and a marked impairment of occupational, social and relationship functioning. MDD disproportionately affects women, and a WHO cross-cultural primary care study found an average sex ratio of 2:1 for current and lifetime depressive episodes. [4]

Depression During Pregnancy

Depressive symptoms occur in approximately 20% of pregnant women, [5] with major depressive episodes (MDEs) occurring in 13% of pregnant women. [6–8] With approximately 4 million live births each year in the USA, this translates to approximately half a million pregnancies being exposed to depression per year. The risk is higher in women who have a history of recurrent MDD prior to pregnancy with a relapse rate of almost 70% in women who discontinue antidepressants for pregnancy. [6] Unfortunately, pregnant women with mental illness are less likely to access care. A recent study reported that only 6% of women needing referral for perinatal mental illness remained in treatment at 6 months, with pregnant women being less likely to follow-up than postpartum women. [9]

Maternal health is a key component of child health. Depressed women may have difficulty caring for themselves in ways necessary to ensure the health of their developing fetus. Women who are depressed during pregnancy are less likely to get prenatal care and more likely to abuse drugs and alcohol. [3,4,10–13] Common symptoms of depression, such as poor sleep and decreased appetite, may also have an adverse impact on pregnancy. Suicidal ideation during pregnancy is unexpectedly high. [14] In addition, depression during pregnancy is associated with poorer obstetrical outcomes such as preterm birth, [15,16] pre-eclampsia, [17] decreased birth weight [18,19] and increased admission to neonatal care units. [20] Importantly, depression during pregnancy usually continues into the postnatal period [21] when maternal depression is known to have adverse effects on mother–infant bonding as well as child development and behavior. [22–27]

Treatment Issues

With respect to the treatment of MDEs during pregnancy, practitioners should know that the current vanguard of evidence exists as consensus practice guidelines, produced by combined task forces of the American Psychiatric Association (APA) and the American College of Obstetricians and Gynecologists (ACOG). [28,29] Available guidelines inform both primary care providers and mental health providers. Providers are instructed to weigh several factors in choosing an appropriate therapy, including whether the individual was taking medication at the time of assessment, the severity of symptoms, and past response to psychotherapy. Primary providers are urged to collaborate with mental health providers when patients demonstrate severe symptoms – suicidal ideation, psychosis, mania or bipolar depression, psychiatric comorbidity or a history of poor response to psychotherapy. Providers should also emphasize healthy lifestyle choices, prenatal education, and screening and treatment of comorbid addictions. Psychotherapy, antidepressants and electroconvulsive therapy are all addressed in the guidelines as potential treatment options.

Amongst all treatment options, pharmacologic antidepressant treatments have been the subject of closest scrutiny. While a thorough review of the numerous issues raised by the pharmacological treatment of depression in pregnancy is beyond the scope of this article, we refer to several sources that have addressed this issue. [16,28–33] Briefly, the majority of research has focused on the risks of antidepressant medication to the developing fetus, and available data suggest serotonin-reuptake inhibitors (SSRIs) and tricyclic antidepressants do not increase rates of major congenital malformations, [29,34,35] although concerns have arisen surrounding reports of low but significant rates of SSRI-attributed cardiac septal defects, [36] persistent pulmonary hypertension of the newborn, [30,32] preterm birth [16,33] and neonatal withdrawal. [31] Conclusive data regarding the fetal risks of pharmacologic treatments are currently unavailable, and available reports have yet to show consistency in these rates. The use of antidepressants during pregnancy requires an evaluation of the risks and benefits for each patient. [15] While fetal safety concerns have drawn the most scientific attention, the efficacy of antidepressant medications during pregnancy remains an understudied issue, with no available randomized placebo-controlled trials. Pregnant women with depression represent a challenging and important study population for multiple reasons, including ethical issues [37,38] and variable pharmacokinetics of the pregnant state. [39,40]

Clinically, when pregnant women are surveyed regarding their treatment preferences for depression, medications are reported to be their least acceptable option. [41–43] Women who are given antidepressants during pregnancy are often treated at inadequate doses, exposing the fetus to a harm profile without any clear therapeutic effect. In addition, it must be acknowledged that the majority of women on antidepressants discontinue use at conception, [44] potentially leading to fetal harm via documented risks of undertreated maternal depression.

There are data supporting psychotherapy as a robust treatment for depression during pregnancy. Two randomized controlled studies have shown interpersonal therapy to be efficacious for mild [45] and moderate [46] depression during pregnancy. There are no randomized or controlled trials of psychodynamic psychotherapy or psychoanalysis to support their use in this special population, owing partly to the difficulty in designing studies to assess these interventions. Despite widespread use in nonpregnant populations, cognitive behavioral therapy has not been studied in pregnancy, although studies are currently underway. [47] Current guidelines suggest psychotherapy be considered as a primary treatment option for depression during pregnancy, [28] and availability of treatment, a low side-effect burden and purported efficacy make psychotherapy a viable treatment option in this population. However, access to skilled practitioners may be an issue in some geographical areas and patients presenting with severe depressive symptoms may not be appropriate for psychotherapy without psychopharmacologic intervention.

An option for women with severe MDD is electroconvulsive therapy (ECT). While there have been no randomized controlled trials clarifying its efficacy or safety in MDD during pregnancy, a recent extensive case review by Anderson et al. provides some evidence in this regard. [48] Anderson et al. looked at 57 articles from 1941–2007, which reported on 339 individuals who received ECT during pregnancy. Of the subpopulation that was treated for MDD without psychosis, 84% were found to experience 'at least a partial response'. There were 11 reported fetal deaths, with one directly attributed to ECT, whereby a woman experienced ECT-induced status epilepticus. The most common adverse fetal effect was a transient bradyarrythmia. In addition to confusion, headache, amnesia and muscle soreness, 3.5% of women experienced uterine contractions or preterm labor. Similar to its role in the treatment of MDD in the general population, ECT is best considered a second-line treatment to be judiciously used in cases requiring urgent symptomatic relief, including women who are experiencing co-occurring psychosis, catatonia or disabling levels of suicidality.

Complementary and herbal medicines represent pharmacologic treatment alternatives for depression and are thought to have fewer adverse effects, although there is little scientific affirmation of this claim. Freeman recently reviewed complementary and alternative medicine strategies for perinatal (all times during and after pregnancy) depression, finding omega-3 fatty acid supplementation to be the most studied approach. [49] Her review concluded that exercise, omega-3 fatty acids and folic acid are promising treatment options in antepartum depression given their probable safety and potential efficacy, warranting more conclusive studies. While none of the studies reviewed studied severe depression, it is unlikely that monotherapy with complementary and herbal medicines would be adequate treatment of moderate to severe MDEs.

Nonpharmacologic treatment options for depressed pregnant women comprise an important and active area of research. Below, we discuss current data regarding these options.

Exercise

In addition to cardiovascular and general health benefits, there is growing evidence that exercise may help alleviate symptoms of mild depression. [50,51] In nonpregnant depression, randomized controlled studies have compared exercise to a control condition, with five of those trials reporting long-term follow-up data. [52–56] Two recent systematic reviews of exercise therapy have shown modest results, including a recent Cochrane review that found an effect size (measured by standardized mean difference) of -0.82 (95% CI: -1.12– -0.51) for the antidepressant effect of exercise. In the same study, post hoc examination of two trials that compared exercise to antidepressant medication (sertraline) revealed an effect size of -0.04 (95% CI: -0.31–0.24), suggesting therapeutic equivalence in these studies. Sensitivity analysis showed that when the review was limited to trials with adequate allocation concealment, intention-to-treat analysis, and blinded outcome assessment, the effect size of exercise shrank to a statistically insignificant -0.42 (95% CI: -0.88–0.03). [57,58]

There are two studies that examine the mood-elevating properties of exercise during pregnancy (Table 1). [59,60] The first study by Lox et al. enrolled women in the second and third trimester of pregnancy into a 6-week semi-weekly 45-min aquatic exercise class. [59] Women were not selected for or screened for MDD. The authors employed a 12-item Subjective Exercise Experiences Scale, which was comprised of subscales measuring positive wellbeing, psychological distress and fatigue. [61] This study found large effect sizes showing improvement in positive wellbeing, moderate effect sizes on psychological distress, and a large reduction of fatigue in the second trimester, an effect that was less significant in subjects in the third trimester of pregnancy. The second study by Polman et al. studied 66 pregnant women between 22 and 41 years of age in the second or third trimester of pregnancy. [60] Women were chosen from four locations, including women participating in either aqua or studio exercise (the experimental group), or a control condition consisting of women enrolled in parentcraft classes or a routine visit with a general practitioner surgeon. Parentcraft classes were designed to prepare women for labor using relaxation techniques and breathing exercises, and the general practitioner surgery group included women who had received care in a surgery clinic and would be following up. Women were asked to complete a profile of mood state before and after each activity. [62] An increase in overall mood scores was seen for participation in aqua and studio conditions, with post hoc analysis showing aquatic exercise was associated with a decrease in the depression sub-score. Parentcraft classes did not alter mood states, and results from the general practitioner surgery group were not explicitly reported. While both studies reveal mood-elevating properties of antepartum exercise, neither study targeted women diagnosed with MDD, employed objective rating scales of depression or adequately controlled for effects of social support.

Table 1. Characteristics of studies looking at the effect of exercise, phototherapy and acupuncture for depression in pregnant women.

Study (year)

Intervention

Duration/design

Women (n)

Axis I diagnosis/inclusion criteria

Outcome

Ref.

Exercise

Lox et al. (2000)

45 min of aquatic aerobic exercise

6-week trial, pre-/post-exercise feeling states

44

No mood disorder diagnosed; pregnant womenin second orthird trimester

Aquatic exercise led to positive feeling states and reductions in both negative feeling statesand fatigue

[59]

Polman et al. (2007)

45–50 min water/studio/parenting classes vs controls

Single session pre-/post-exercise mood-state evaluation

66

No mood disorder diagnosed; pregnant women in second or third trimester

Aqua and studio classes improved mood and increased vigor, aqua decreased depression subscore of POMS

[60]

Phototherapy

Oren et al. (2002)

60 min bright light therapy

3–5 weeks, open trial, A–B–A design

16

DSM-IV MDD; pregnant women mean gestational age 23 weeks

Depression ratings monitored by SIGH-SAD improved by 49%

[71]

Epperson et al. (2004)

60 min of AM 500 lux (placebo) or 7000 lux light box

10-week randomized, blinded, controlled trial with crossover

10

DSM-IV MDD; pregnant women gestational age 8–32 weeks

In 5-week trial, SIGH-SAD ratings were not statistically different; however, at 10 weeks, there was a significant treatment effect; adjustments were needed to accommodate one episode of emergent hypomania

[73]

Acupuncture

Manber et al. (2004)

Active acupuncture vs control acupuncture vs massage

Semi-blinded, randomized controlled trial, three-arm design

61

MDD, HDRS >14, pregnancy 11–28 weeks

Response rates for active acupuncture (69%) were greater than for control acupuncture (47%) and for massage (32%)

[85]

DSM-IV: Diagnostic and Statistical Manual IV text revision; HDRS: Hamilton Depression Rating Scale; MDD: Major depressive disorder; POMS: Profile of Mood States; SIGH-SAD: Hamilton Depression Rating Scale – Seasonal Affective Disorder version.

As exercise is recommended during pregnancy by the American College of Obstetricians and Gynecologists, the UK Department of Health, and the US Department of Health and Human Services, and healthy lifestyles are encouraged by the combined APA/ACOG treatment guidelines, exercise can be recommended to pregnant women with depression with suggestions that it may have mood-elevating properties. There is currently no evidence that exercise is effective as monotherapy for moderate or severe depressive symptoms or women meeting criteria for MDD during pregnancy. Women who are hesitant to take medication or enter psychotherapy may chose exercise as a treatment for depression, and further study of this option would inform treating clinicians. Published recommendations for exercise during pregnancy are summarized in Table 2, although these recommendations should not replace consultation with an obstetrical provider in cases of concern and for practical suggestions for safe exercises. [28,63–65]

Table 2. Governing body recommendations for exercise during pregnancy.

Agency

Recommendations

ACOG

Exercise is not recommended if a woman has risk factors for preterm labor, vaginal bleeding or premature ruptureof membranes

Safe exercises, even for women who do not exercise before pregnancy, include walking, swimming, cycling and aerobics

In women who are active before pregnancy, running, racquet sports and strength training may be safe to continue in moderation

Downhill skiing, contact sports and scuba diving should be avoided

If just beginning to exercise, women should start with 5 min of exercise a day and add 5 min each week until 30 min of activity a day is tolerable

Avoid exercises that require lying prone after the first trimester and exercises that may cause overheating or dehydration

DH-UK

If inactive before pregnancy, do not suddenly start strenuous exercise

Try to keep active on a daily basis. Build in half an hour of activities a day, such as walking, keeping in mind any amount is better than nothing

Avoid strenuous exercise in hot weather

If attending exercise classes, ensure the instructor is qualified and aware of the pregnancy and gestational age

Swimming will support increased weight, and many pools offer aquanatal classes

HHS-US

Healthy women who are not already highly active or doing vigorous-intensity activity should get at least 150 min of moderate-intensity aerobic activity per week during pregnancy and the postpartum period. Preferably, this activity should be spread throughout the week

Pregnant women who habitually engage in vigorous-intensity aerobic activity or are highly active can continue physical activity during pregnancy and the postpartum period, provided that they remain healthy and discuss with their healthcare provider how and when activity should be adjusted over time

ACOG: American College of Obstetricians and Gynecologists; DH-UK: United Kingdom Department of Health; HHS-US: United States Department of Health and Human Services.

Phototherapy (Bright Light Therapy)

While recognized as an effective treatment in seasonal affective disorder (SAD), [66] there is also evidence that light therapy is therapeutic in non-SADs. [67,68] Studies have examined the therapeutic role of light therapy both as monotherapy for MDD and as an adjunct to pharmacotherapy. Data suggest that light therapy in either role may be therapeutic, but recent systematic reviews have not shown this conclusively. [67–69] Studies that used morning light treatment and targeted sleep deprivation responders showed better efficacy data. In an attempt to review the safety of light therapy for depression, Lam et al. retrospectively studied suicidality in 191 nonpregnant patients with SAD who received light therapy for their depression. [70] Patients were rated using the Structured Interview Guide for the Hamilton Depression Rating Scale (HDRS), Seasonal Affective Disorder Version (SIGH-SAD), which includes an eight-item supplemental scale for 'atypical' depressive symptoms, and the authors focused on one suicidality item, scored from 0–4, describing a range from feelings of worthlessness to attempts at suicide. This study found that 45% (85 of 191) of patients had a reduction in the suicide item (p < 0.001), while 3% (six of 191) of patients reported a higher suicide score after treatment and no patients reported a suicide attempt. Overall, 67% (128 of 191) patients were rated as treatment responders, and SIGH-SAD scores decreased by a mean of 56 ± 24%.

Given the low risk to the fetus, two studies have looked at the efficacy of light therapy in treating depression in pregnancy (Table 1). Oren et al. used a prospective, open trial with an A–B–A design (pretreatment – active treatment – post-treatment) to explore the effect of 60 min of 10,000-lux morning light exposure on 16 women meeting Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for MDD. [71] The primary outcome measure was an augmented version of the 21-item HDRS SIGH-SAD. [72] The mean age of women in this study was 34 years, all patients were Caucasian, and women were on average 23 weeks pregnant. They found that after 3 weeks of treatment, the average reduction in SIGH-SAD was 49%, with 50% (eight of 16) of patients experiencing a reduction in SIGH-SAD of 50% or greater. For patients that underwent 5 weeks of treatment, 57% (four of seven) patients had at least 50% reduction in SIGH-SAD with a final absolute score less than 8, crossing a common benchmark for complete remission. While these results are encouraging, the study design lacked a control condition.

Extending these findings, the same group proceeded to study 10 women in a randomized trial that included a placebo condition. [73] Women with an average age of 32.1 years and from 8–32 weeks pregnant were recruited through media and local physician referrals. All women met DSM-IV criteria for MDD. The trial included a lead in of 1 week during which all women were instructed to wake up 30 min earlier than they were accustomed to, in an effort to control for the impact of altering the sleep cycle. Subjects were then randomized to receive 60-min daily treatments of either 7000 lux active bright light or 500 lux dim placebo bright light within 10 min of rising for 5 weeks. Daily phone logs monitored compliance. Subjects with a partial response to active light at the end of 5 weeks, defined by a 25–49% decrease in SIGH-SAD, were instructed to increase duration of exposure to 75 min for 5 additional weeks, while placebo nonresponders could choose a 5-week trial of active therapy. After 5 weeks, there was a nonsignificant trend in improvement in the active group compared to the placebo group. The overall small size of the study may have contributed to inability to detect a group difference.

While available research is not conclusive, light therapy remains a promising treatment for MDD. However, there are not enough data to be able to conclusively recommend this as an evidence-based treatment for depression during pregnancy. If psychotherapy or antidepressants are not an option for a particular patient with a mild-to-moderate MDE, a course of light therapy may be of benefit, with no documented risk to the fetus, and perhaps specifically for women with seasonal exacerbation of mood symptoms. Patients should be carefully screened for bipolar disorder prior to prescribing light therapy given the risk of emergent hypomania. [66] Guidelines for prescribing light therapy are summarized in Table 3.

Table 3. Evidence-based guidelines for prescribing phototherapy.

Ref.

Timing

Patients are most likely to benefit from light administered a short interval after waking in the morning

[66]

Dosage

A dosage of 10,000 lux for 30 min has been found to be most effective in SAD in the nonpregnant population.

Two studies in pregnant women used higher doses of light, with treatment duration greater or equal to 60 min in both studies.

[66,71,73]

Wavelength

Broad-spectrum white light from fluorescent lamps is safest while still effective.

[66]

Placement

Patients should sit within several yards of the light box. They can read or perform other activities providing they remember to look at the light box periodically. Staring at the box is not necessary.

Two studies in pregnant women mandated closer placement, asking patients to sit within 13 inches of the light source, with the light source positioned above their heads, pointing down.

[66]

Duration of therapy

Treatment cessation has been linked with rapid relapse in patients with SAD (within 1–2 weeks), leading to recommendations that treatment be continued throughout the period of risk.

[87]

Choosing alight box

Comparative studies looking at benefits of different boxes are lacking; however, the Mayo Clinic offers the following general guidelines for helping a patient chose a light box:

Devices can be purchased online, at some drugstores and even hardware stores without a physician prescription

Ensure the device has been shown to be safe

Find a device designated to treat SAD

Note the distance a person must sit to achieve 10,000 lux

Avoid boxes that do not filter UV light

Cost may range from US$90 to $500 (GB£55 to £300)

[101]

SAD: Seasonal affective disorder.

Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a novel device technology which noninvasively delivers focused magnetic pulses to the surface of the brain. [74,75] When the magnetic pulses reach the cortex the counter-current physical principle of electromagnetism causes local current flow and thus local neuronal depolarization. For depression, TMS is given over the left dorsolateral prefrontal cortex (DLPFC) at a high frequency or over the right DLPFC at low frequency. TMS has been researched as a putative treatment for MDD for just over a decade. In all there have now been over 35 controlled clinical trials. Recent meta-analyses of the database of TMS studies show clear efficacy with an effect size of 0.75 (moderate-to-large) and a very favorable tolerability profile (a discontinuation rate of approximately 5% owing to adverse events in short-term clinical trials). [76] In 2008, the US FDA approved TMS as a new treatment for MDD in patients who fail one adequate antidepressant medication trial. The most common side effect is headache, although rarely seizure, facial numbness and hearing loss have been reported. [77] As no sedation or analgesia is required, TMS offers a potent CNS active treatment without exposing the fetus to the effects of drugs that cross the placenta.

Based on these findings, investigators have begun to look at TMS for depression during pregnancy. To date, there are only six cases in the literature regarding the use of TMS for depression during pregnancy. [78–80] In all cases, maternal depression improved. The first case study regarding the use of TMS in a depressed pregnant woman was published in 1999. Treatment began at week 22 of pregnancy (second trimester). [78] The patient received 14 days of treatment over the course of 3 weeks. Her depression remitted and she delivered a healthy 7.5 lb term infant. There was no change in the patient's blood pressure, oxygen saturation or heart rate during any of the TMS procedures. The next two patients were reported in 2008. [79] One patient received 15 sessions of left DLPFC TMS. The treatments were started at 16 weeks of pregnancy. The second patient started right DLPFC TMS at 31 weeks of pregnancy for 15 sessions. Both patients had greater than 50% reduction in depression scores. One infant was born at 36 weeks but the mother was also taking venlafaxine. Both infants were reported to be healthy but no specific information regarding how this was assessed is given. Most recently, in 2009, an additional three cases were reported. [80] No details concerning the frequency, duration, number of pulses or sessions were given. While details were not provided, the authors made a general statement that the infants were born in 'good health'.

These cases suggest that TMS may eventually be a viable option for depression during pregnancy both as a primary treatment and as an adjunctive treatment. However, these are case reports and to date there has been no systematic study of this hypothesis. TMS, similar to ECT, requires collaboration with a trained behavioral health specialist trained in administering TMS. As with ECT, women are required to attend to a treating facility between three- and five-times per week. However, as TMS does not require any pharmacologic agents and patients can resume daily activities immediately after a treatment session, TMS may provide some practical advantages to patients, with potential efficacy in those who have failed either antidepressant medication or psychotherapy. While TMS cannot be recommended at this time, practitioners are advised to be aware of this treatment as it is likely to be a future option for pregnant women with depression.

Acupuncture

Acupuncture is a treatment alternative with evidence of efficacy in MDD and one rigorous study in pregnancy. The most recent systematic review of acupuncture for depression included 20 trials of acupuncture meeting structured inclusion criteria, describing nearly 2000 nonpregnant patients with depression. [81] Including studies that employed multiple different diagnostic criteria to establish the presence of MDD (DSM, International Statistical Classification of Diseases or Chinese classification of mental disorders), Zhang et al. found that acupuncture had similar outcomes to antidepressant medications. The study was limited by high heterogeneity, inclusion of small studies, and poor characterization of illness. Previous meta-analyses have been plagued by similar problems, generally concluding that there are promising but insufficient data to determine the efficacy of acupuncture in MDD. [82–84]

Manber et al. looked at the antidepressant effect of acupuncture during pregnancy. [85] Study characteristics are summarized in Table 1. They randomly assigned 61 women to one of three interventions: active acupuncture with a treatment plan specifically targeting depression, acupuncture that was not tailored to treat depressive symptoms, and a massage condition included to control for 'attention, physical contact, relaxation and respite from daily stress'. Treatments consisted of 12 sessions over 8 weeks. A double-blinding of acupuncture treatments was established by utilizing two acupuncture providers: one provider was responsible for assessing and designing a treatment plan, another was responsible for needling the prescribed plan. Each plan had an equal number of acupuncture points in similar anatomic locations. Participants were recruited from obstetrician offices and local advertisements. Treatment response was monitored using the 17-itemHDRS, [86] and a classification of response required cessation of symptoms meeting DSM-IV criteria for a MDE, a HDRS reduction of 50% of baseline, and an absolute HDRS less than 14. Overall, they found efficacy for active acupuncture with 68.8% of patients responding to the treatment, while 47.4% of women responded to inactive acupuncture, and 31.6% of women responded to massage therapy. While active acupuncture differed significantly from massage treatment (p = 0.03), it was not statistically differentiated from inactive acupuncture treatment (p = 0.18). They did not report any adverse effects of treatment.

While these findings reflect a nonspecific therapeutic effect of acupuncture in depression during pregnancy, the paucity of evidence does not currently support acupuncture as a treatment recommendation. The safety of acupuncture during pregnancy remains unclear, and attitudes towards acupuncture during pregnancy vary from country to country, with malpractice considerations playing a role.

Conclusion

Depression during pregnancy is an important and prevalent health problem. The costs of untreated depression are shared by both mother and fetus, making safe treatment options invaluable. Our commonest remedies for MDD in the nonpregnant population lack conclusive safety and efficacy data in pregnancy. Practice guidelines lay the groundwork for establishing the importance of treating depression in this population, and have concluded that psychotherapy and antidepressant medications are first-line treatment recommendations. Treatment alternatives add to the clinician's armamentarium, specifically for women who chose to forego psychotherapy and/or antidepressant medications. Options such as exercise or light therapy may provide a treatment alternative with a more acceptable risk profile, although their efficacy remains in question. For severe depression, treatment alternatives such as ECT or TMS may be the most effective and appropriate options available, although neither is FDA approved specifically for treatment during pregnancy.

In considering treatment recommendations, the clinician should consider severity of depression, past psychiatric history, psychiatric comorbidity, patient treatment preferences and the risks of not treating or undertreating maternal depression. In addition, all women with depression should also be screened for bipolar disorder as this diagnosis requires different treatment recommendations. Choosing a treatment option in depression during pregnancy can be a demanding process and consultation with a behavioral health specialist with expertise in reproductive issues is strongly urged, especially in cases where suicidal ideation, mania, psychosis or other significant psychiatric comorbidity is present. Particular attention should be given to adequately attaining informed consent.

For patients with a milder depression, complementary/alternative treatments offer therapeutic alternatives that often have known generalized benefits for mother and fetus and are generally accepted as safe, although efficacy in severe depression remains in doubt. As Freeman concluded in her review, exercise, omega-3 fatty acids and folic acid are three such options that can be easily added to any regimen with few risks, with the potential to alleviate mild-to-moderate MDE symptoms, but no conclusive evidence as of yet. [49]

In specific situations, a patient's depressive symptoms may warrant targeted treatment options. In expecting mothers with a history of seasonal mood symptoms, bright light therapy may be the most appropriate treatment alternative available. Similarly, for catatonic and psychotic depression, ECT would be a conspicuous choice. Women with a proclivity for traditional medicine remedies may find acupuncture to be a suitable treatment alternative. TMS remains an exciting and potentially valuable tool for treating antepartum depression, but more data are needed before it can be recommended.

Future Perspective

The culmination of safety studies looking at antidepressant medications is likely to result in low but established rates of teratogenicity and perinatal complications. Further epidemiologic data will likely establish the low but significant rate of complications related to untreated depression during pregnancy and add to the importance of the availability of lower or negligible-risk treatment alternatives. Women burdened with decisions informed by these studies may opt to undergo treatment for depression, but find any documented fetal risk to be unsatisfactory. Research on alternative treatments for depression should expand upon current findings, showing exercise therapy, phototherapy and accupuncture to be effective treatment strategies for depression with studied effect sizes similar to those for pharmaceutical and psychotherapeutic treatments for mild-to-moderate depression. Further studies of ECT will help quantify its perinatal risks, and inform the cost–benefit decisions made for the treatment of severe MDEs. Controlled trials of TMS in pregnant women will likely mirror the moderate to large effect sizes already shown for MDD, potentially offering pregnant women a time-intensive but safe procedure for more treatment-refractory MDEs.

Sidebar

Executive Summary

Depression & depression during pregnancy

Major depressive disorder (MDD) is a common disorder defined by the Diagnostic and Statistical Manual of Mental Disorders IV, ranging in severity from mild to severe.

Antepartum depression is an important and widespread health problem.

Clinically significant depression occurs in approximately 13% of pregnant women.

Depression conveys adverse risks including poorer obstetrical outcomes and elevated risk for postpartum depression.

Treatment issues

American Psychiatric Association (APA)/ American College of Obstetricians and Gynecologists (ACOG) consensus treatment guidelines represent the gold standard of treatment for depression during pregnancy.

Our commonest remedies for major depressive disorder in the nonpregnant population lack conclusive safety and efficacy data in pregnancy, and antidepressant medications likely have low but appreciable adverse effect profiles in pregnant women.

Pregnant women are often hesitant to take antidepressant medications.

Complementary and herbal medicines (folic acid, omega-3 fatty acids) have been studied as potential treatment alternatives.

Psychotherapy has shown efficacy as a treatment option for mild-to-moderate antepartum MDD.

ECT remains an option for severe depressive episodes, often used for depression with psychotic features, catatonic depression or disabling levels of suicidality.

Untreated or undertreated depression likely conveys risks to both maternal and child health.

Exercise therapy

Exercise therapy for MDD has been the subject of much research in nonpregnant populations, and outcomes suggest modest effects, though study quality has been questioned.

Studies of exercise therapy in antepartum MDD are lacking.

The only data currently available suggest that exercise may have short-term mood elevating properties in nondepressed pregnant women.

Exercise is recommended during all pregnancies as part of healthy lifestyle recommendations.

Further research is needed to target this as a potential therapy for antepartum MDD.

Phototerapy

Phototherapy has been shown to be effective for seasonal affective disorder, and studies in nonpregnant populations suggest efficacy in MDD.

Two small, well-designed studies suggest a therapeutic effect on depressive symptoms in antepartum MDD.

Risks include a potential increase in suicidality and treatment-emergent hypomania.

Conclusive data are lacking, though phototherapy remains a conspicuous choice for antepartum depression that follows a historically seasonal pattern.

Transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is an US FDA-approved treatment for MDD in patients who have failed one adequate antidepressant medication trial.

Evidence for TMS for antepartum MDD comes from six case reports, none reporting adverse effects.

TMS necessitates collaboration with a trained behavioral health specialist, and is time intensive, requiring women to come between 3–5 times per week to a treating facility.

Potential benefits of TMS include the avoidance of pharmacotherapy and potential efficacy in more refractory MDEs.

Acupuncture

Studies have shown efficacy of acupuncture in MDD.

One study targeting antepartum MDD compared active (MDD-targeted) acupuncture to inactive (non-MDD-targeted) treatment to massage treatment, finding both active and inactive treatments resulting in significant improvement over massage; however, active treatment was not statistically superior to inactive treatment.

Attitudes toward acupuncture vary geographically, and acupuncturists are under similarly variable malpractice constraints.

Conclusion

APA/ACOG Practice Guidelines are the gold standard for the treatment of antepartum MDD.

Women should be informed of the risks of undertreated depression.

Exercise, phototherapy, TMS and acupuncture cannot be recommended as first-line treatments in antepartum depression based on current evidence.

Further study is needed to establish safe treatment options for depressed women who are reluctant or unable to take antidepressant medications or undergo psychotherapy.

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Website
101. Mayo Clinic Staff: Seasonal affective disorder treatment: choosing a light therapy box www.mayoclinic.com/health/seasonalaffective-disorder-treatment/DN000132009 (Accessed 21 May 2009)

Papers of special note have been highlighted as:
• of interest
•• of considerable interest

Financial & competing interests disclosure
Deborah Kim has received support from Neuronetics, Inc.The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.

Women's Health. 2010;6(4):565-576. © 2010 Future Medicine Ltd.

Authors and Disclosures

Christopher Tjoa †1 , Emmanuelle Pare 2 & Deborah R Kim 1

1 Department of Psychiatry, 3535 Market St, 2nd Floor, Philadelphia, PA 19104, USA
2 Department of Obstetrics & Gynecology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

† Author for correspondence
Tel.: +1 215 746 7235 Fax: +1 215 573 5668 chris.tjoa@uphs.upenn.edu

-From: Medscape Psychiatry, July 20, 2010, http://www.medscape.com/viewarticle/724835_9, retrieved 7/21/10.

7/10

Study (year)	Intervention	Duration/design	Women (n)	Axis I diagnosis/inclusion criteria	Outcome	Ref.
Exercise
Lox et al. (2000)	45 min of aquatic aerobic exercise	6-week trial, pre-/post-exercise feeling states	44	No mood disorder diagnosed; pregnant womenin second orthird trimester	Aquatic exercise led to positive feeling states and reductions in both negative feeling statesand fatigue	[59]
Polman et al. (2007)	45–50 min water/studio/parenting classes vs controls	Single session pre-/post-exercise mood-state evaluation	66	No mood disorder diagnosed; pregnant women in second or third trimester	Aqua and studio classes improved mood and increased vigor, aqua decreased depression subscore of POMS	[60]
Phototherapy
Oren et al. (2002)	60 min bright light therapy	3–5 weeks, open trial, A–B–A design	16	DSM-IV MDD; pregnant women mean gestational age 23 weeks	Depression ratings monitored by SIGH-SAD improved by 49%	[71]
Epperson et al. (2004)	60 min of AM 500 lux (placebo) or 7000 lux light box	10-week randomized, blinded, controlled trial with crossover	10	DSM-IV MDD; pregnant women gestational age 8–32 weeks	In 5-week trial, SIGH-SAD ratings were not statistically different; however, at 10 weeks, there was a significant treatment effect; adjustments were needed to accommodate one episode of emergent hypomania	[73]
Acupuncture
Manber et al. (2004)	Active acupuncture vs control acupuncture vs massage	Semi-blinded, randomized controlled trial, three-arm design	61	MDD, HDRS >14, pregnancy 11–28 weeks	Response rates for active acupuncture (69%) were greater than for control acupuncture (47%) and for massage (32%)	[85]

Agency	Recommendations
ACOG	Exercise is not recommended if a woman has risk factors for preterm labor, vaginal bleeding or premature ruptureof membranes Safe exercises, even for women who do not exercise before pregnancy, include walking, swimming, cycling and aerobics In women who are active before pregnancy, running, racquet sports and strength training may be safe to continue in moderation Downhill skiing, contact sports and scuba diving should be avoided If just beginning to exercise, women should start with 5 min of exercise a day and add 5 min each week until 30 min of activity a day is tolerable Avoid exercises that require lying prone after the first trimester and exercises that may cause overheating or dehydration
DH-UK	If inactive before pregnancy, do not suddenly start strenuous exercise Try to keep active on a daily basis. Build in half an hour of activities a day, such as walking, keeping in mind any amount is better than nothing Avoid strenuous exercise in hot weather If attending exercise classes, ensure the instructor is qualified and aware of the pregnancy and gestational age Swimming will support increased weight, and many pools offer aquanatal classes
HHS-US	Healthy women who are not already highly active or doing vigorous-intensity activity should get at least 150 min of moderate-intensity aerobic activity per week during pregnancy and the postpartum period. Preferably, this activity should be spread throughout the week Pregnant women who habitually engage in vigorous-intensity aerobic activity or are highly active can continue physical activity during pregnancy and the postpartum period, provided that they remain healthy and discuss with their healthcare provider how and when activity should be adjusted over time

		Ref.
Timing	Patients are most likely to benefit from light administered a short interval after waking in the morning	[66]
Dosage	A dosage of 10,000 lux for 30 min has been found to be most effective in SAD in the nonpregnant population. Two studies in pregnant women used higher doses of light, with treatment duration greater or equal to 60 min in both studies.	[66,71,73]
Wavelength	Broad-spectrum white light from fluorescent lamps is safest while still effective.	[66]
Placement	Patients should sit within several yards of the light box. They can read or perform other activities providing they remember to look at the light box periodically. Staring at the box is not necessary. Two studies in pregnant women mandated closer placement, asking patients to sit within 13 inches of the light source, with the light source positioned above their heads, pointing down.	[66]
Duration of therapy	Treatment cessation has been linked with rapid relapse in patients with SAD (within 1–2 weeks), leading to recommendations that treatment be continued throughout the period of risk.	[87]
Choosing alight box	Comparative studies looking at benefits of different boxes are lacking; however, the Mayo Clinic offers the following general guidelines for helping a patient chose a light box: Devices can be purchased online, at some drugstores and even hardware stores without a physician prescription Ensure the device has been shown to be safe Find a device designated to treat SAD Note the distance a person must sit to achieve 10,000 lux Avoid boxes that do not filter UV light Cost may range from US$90 to $500 (GB£55 to £300)	[101]